Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

Abstract:

:Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Shim SY,Jeong HJ,Park HJ,Kwon EY,Kim BM,Choi YJ,Choi YH,Cho SJ,Choi JH,Park EA

doi

10.1038/s41598-017-06401-x

subject

Has Abstract

pub_date

2017-07-20 00:00:00

pages

6052

issue

1

issn

2045-2322

pii

10.1038/s41598-017-06401-x

journal_volume

7

pub_type

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